chr3-53871420-G-A

Variant names:

• chr3-53871420-G-A
• rs1030608705
• NM_022899.5:c.1379C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_022899.5(ACTR8):​c.1379C>T​(p.Ser460Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ACTR8 NM_022899.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.88
• Publications: 1 publications found

Genes affected

ACTR8 (HGNC:14672): (actin related protein 8) Predicted to enable ATP binding activity. Predicted to be involved in chromatin remodeling; double-strand break repair; and regulation of transcription, DNA-templated. Located in centrosome and nucleoplasm. Part of Ino80 complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022899.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACTR8	NM_022899.5	MANE Select	c.1379C>T	p.Ser460Phe	missense	Exon 11 of 13	NP_075050.3
	ACTR8	NM_001410774.1		c.1046C>T	p.Ser349Phe	missense	Exon 11 of 13	NP_001397703.1	Q9H981-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACTR8	ENST00000335754.8	TSL:2 MANE Select	c.1379C>T	p.Ser460Phe	missense	Exon 11 of 13	ENSP00000336842.3	Q9H981-1
	ACTR8	ENST00000888053.1		c.1379C>T	p.Ser460Phe	missense	Exon 11 of 13	ENSP00000558112.1
	ACTR8	ENST00000963856.1		c.1379C>T	p.Ser460Phe	missense	Exon 11 of 14	ENSP00000633915.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461858 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727226

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112004

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.037	T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.084	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Uncertain	0.71	D
MutationAssessor	Uncertain	2.2	M
PhyloP100		6.9
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.41
Sift	Uncertain	0.024	D
Sift4G	Uncertain	0.060	T
Polyphen		0.79	P
Vest4		0.52
MutPred		0.33		Loss of phosphorylation at S460 (P = 0.0194)
MVP		0.97
MPC		0.72
ClinPred		0.90	D
GERP RS		5.9
Varity_R		0.13
gMVP		0.43
Mutation Taster		=47/53	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1030608705; hg19: chr3-53905447; COSMIC: COSV99213887; COSMIC: COSV99213887;